Interactions Between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis and Innate Immunity

Abstract

Hepatitis C virus (HCV) causes a persistent chronic infection of hepatocytes resulting in progressive fibrosis and carcinogenesis. Abnormalities in mitochondria are prominent features of clinical disease where ultrastructural changes, alterations in electron transport, and excess reactive oxygen species production occur. These mitochondrial abnormalities correlate with disease severity and resolve with viral eradication. Multiple viral proteins, particularly core and NS3/4a bind to mitochondria. The core and NS5a proteins primarily cause ER stress, ER Ca 2+ release and enhance direct transfer of Ca 2+ from ER to mitochondria. This results in electron transport changes, increased ROS production, and sensitivity to mitochondrial permeability transition and cell death. The viral protease, NS3/4a, binds to mitochondria as well where it cleaves an important signaling adapter, MAVS, thus preventing viral clearance by endogenous interferon production. This review discusses the mechanisms by which HCV causes mitochondrial changes and consequences of these for disease.